Tumor growth is absolutely dependent upon angiogenesis. Prior to the development of breast cancer, the breast tissue in many women undergoes progressive changes which include proliferative breast disease and carcinoma in situ. We examined these pathologic changes for the level of vascularity and the presence of angiogenic growth factors in the hopes of identifying targets for chemoprophylaxis. To date, we have shown that angiogenesis begins in the earliest stages of progression. In addition, even normal breast tissue contains numerous angiogenic factors; however, these are insufficient to induce angiogenesis. Using an in vitro organ culture system of normal breast tissue, we found that exogenous angiogenic factors were unable to stimulate endothelial cell proliferation. Furthermore, under nonstimulated conditions, endothelial cell proliferation was restricted to the adipose tissue and perilobular connective tissue. The endothelium within the fibrous stroma could almost never be induced to proliferate. We are now examining normal breast epithelium and stroma for the presence of angiogenic inhibitors. Angiogenic potential in this tissue appears to be the result of an interplay of angiogenic stimulators and inhibitors.

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